{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:33:33Z","timestamp":1791261213113,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P021220\/1"],"award-info":[{"award-number":["MR\/P021220\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R502364\/1"],"award-info":[{"award-number":["MR\/R502364\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The relative role of skeletal muscle mechano\u2010transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6\u00a0weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Non\u2010hypogonadal men (<jats:italic>n<\/jats:italic>\u00a0=\u00a016; 18\u201330\u00a0years) were randomized in a double\u2010blinded fashion to receive placebo (P, saline <jats:italic>n<\/jats:italic>\u00a0=\u00a08) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a08], injections, before 6\u00a0weeks of supervised whole\u2010body RET. Participants underwent dual\u2010energy X\u2010ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Zoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4\u00a0\u00b1\u00a02.8 to 55.8\u00a0\u00b1\u00a03.1\u00a0kg, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.61 vs. P: 55.9\u00a0\u00b1\u00a01.7 to 57.4\u00a0\u00b1\u00a01.7\u00a0kg, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.006, effect size (ES)\u00a0=\u00a00.31], composite strength (Z: 40\u00a0\u00b1\u00a02.3% vs. P: 49.8\u00a0\u00b1\u00a03.3%, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.03, ES\u00a0=\u00a01.4), and muscle thickness (Z: 2.7\u00a0\u00b1\u00a00.4 to 2.69\u00a0\u00b1\u00a00.36\u00a0cm, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.99 vs. P: 2.74\u00a0\u00b1\u00a00.32 to 2.91\u00a0\u00b1\u00a00.32\u00a0cm, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001, ES\u00a0=\u00a00.48) gains. Hypogonadism attenuated molecular transducers of muscle growth related to T metabolism (e.g. <jats:italic>androgen receptor<\/jats:italic>: Z: 1.2 fold, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.99 vs. P: 1.9 fold, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001, ES\u00a0=\u00a00.85), anabolism\/myogenesis (e.g. <jats:italic>IGF\u20101Ea<\/jats:italic>: Z: 1.9 fold, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.5 vs. P: 3.3 fold, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.0005, ES\u00a0=\u00a00.72; <jats:italic>IGF\u20101Ec<\/jats:italic>: Z: 2 fold, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.99 vs. P: 4.7 fold, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.0005, ES\u00a0=\u00a00.68; myogenin: Z: 1.3 fold, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.99 vs. P: 2.7 fold, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.002, ES\u00a0=\u00a00.72), RNA\/DNA (Z: 0.47\u00a0\u00b1\u00a00.03 to 0.53\u00a0\u00b1\u00a00.03, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.31 vs. P: 0.50\u00a0\u00b1\u00a00.01 to 0.64\u00a0\u00b1\u00a00.04, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.003, ES\u00a0=\u00a00.72), and RNA\/ASP (Z: 5.8\u00a0\u00b1\u00a00.4 to 6.8\u00a0\u00b1\u00a00.5, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.99 vs. P: 6.5\u00a0\u00b1\u00a00.2 to 8.9\u00a0\u00b1\u00a01.1, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.008, ES\u00a0=\u00a00.63) ratios, as well as acute RET\u2010induced phosphorylation of growth signalling proteins (e.g. AKT<jats:sup>ser473<\/jats:sup>: Z: 2.74\u00a0\u00b1\u00a00.6, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.2 vs. P: 5.5\u00a0\u00b1\u00a01.1 fold change, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, ES\u00a0=\u00a00.54 and mTORC1<jats:sup>ser2448<\/jats:sup>: Z: 1.9\u00a0\u00b1\u00a00.8, <jats:italic>P<\/jats:italic>\u00a0&gt;\u00a00.99 vs. P: 3.6\u00a0\u00b1\u00a01 fold change, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.002, ES\u00a0=\u00a00.53). Both MPS (Z: 1.45\u00a0\u00b1\u00a00.11 to 1.50\u00a0\u00b1\u00a00.06%\u00b7day<jats:sup>\u22121<\/jats:sup>, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.99 vs. P: 1.5\u00a0\u00b1\u00a00.12 to 2.0\u00a0\u00b1\u00a00.15%\u00b7day<jats:sup>\u22121<\/jats:sup>, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.01, ES\u00a0=\u00a00.97) and (extrapolated) muscle protein breakdown (Z: 93.16\u00a0\u00b1\u00a07.8 vs. P: 129.1\u00a0\u00b1\u00a013.8\u00a0g\u00b7day<jats:sup>\u22121<\/jats:sup>, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.04, ES\u00a0=\u00a00.92) were reduced with hypogonadism result in lower net protein turnover (3.9\u00a0\u00b1\u00a01.1 vs. 1.2\u00a0\u00b1\u00a01.1\u00a0g\u00b7day<jats:sup>\u22121<\/jats:sup>, <jats:italic>P\u00a0=<\/jats:italic>\u00a00.04, ES\u00a0=\u00a00.95).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that endogenous T sufficiency has a central role in the up\u2010regulation of molecular transducers of RET\u2010induced 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